title: The chromatin remodelling complex NoRC safeguards genome stability by heterochromatin formation at telomeres and centromeres.
abstract: Constitutive heterochromatin is crucial for the integrity of chromosomes and genomic stability. Here, we show that the chromatin remodelling complex NoRC, known to silence a fraction of rRNA genes, also establishes a repressive heterochromatic structure at centromeres and telomeres, preserving the structural integrity of these repetitive loci. Knockdown of NoRC leads to relaxation of centromeric and telomeric heterochromatin, abnormalities in mitotic spindle assembly, impaired chromosome segregation and enhanced chromosomal instability. The results demonstrate that NoRC safeguards genomic stability by coordinating enzymatic activities that establish features of repressive chromatin at centromeric and telomeric regions, and this heterochromatic structure is required for sustaining genomic integrity.
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, INF 581, D-69120 Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Postepska-Igielska
authors.forename: Damir
authors.initials: D
authors.lastname: Krunic
authors.forename: Nina
authors.initials: N
authors.lastname: Schmitt
authors.forename: Karin M
authors.initials: KM
authors.lastname: Greulich-Bode
authors.forename: Petra
authors.initials: P
authors.lastname: Boukamp
authors.forename: Ingrid
authors.initials: I
authors.lastname: Grummt
mesh_terms: D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D005786:Gene Expression Regulation; D020459:Genes, rRNA; D042822:Genomic Instability; D006367:HeLa Cells; D006570:Heterochromatin / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D034741:RNA, Small Interfering / Q000235:genetics; D016615:Telomere / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
chemical_list: D001324:Autoantigens; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D034741:RNA, Small Interfering; C436708:BAZ2A protein, human; D000092468:Bromodomain Containing Proteins